The research aim of the project is to study the mechanisms by which the spatial inhomogenities of membrane properties and cell-cell coupling determine the normal and abnormal activation sequence of the heart. The specific focus of this research is the junctional region between Purkinje (P) cells and the underlying Ventricular (V) endocardium. The techniques used include both numerical simulation of action potential propagation and experimental mapping of P and V activation sequences. The particular relevance of these studies is that the junctional region between P cells and V cells not only forms an essential part of the normal cardiac excitation sequence, but may also be involved in the abnormal excitation sequences produced under ischemic conditions. Our hypothesis is that the activation sequence is determined not only by differences in excitability between P cells and V cells, but also by particular spatial distribution of partial electrical uncoupling between the two cell layers.